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Overview of papillary thyroid cancer

Author
R Michael Tuttle, MD
Section Editor
Douglas S Ross, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Thyroid follicular epithelial-derived cancers include papillary, follicular, and anaplastic cancer. Papillary and follicular cancers are considered differentiated cancers, and patients with these tumors are often treated similarly despite numerous biologic differences. The general pathogenetic, pathologic, and prognostic features of papillary thyroid cancer and its variants will be discussed here. The treatment of well-differentiated thyroid cancers and an overview of follicular thyroid cancer are discussed separately. (See "Differentiated thyroid cancer: Overview of management" and "Overview of follicular thyroid cancer".)

INCIDENCE

In a report based upon the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2012, the incidence of papillary cancer increased from 4.8 to 14.9 per 100,000 (figure 1) [1]. In 2012, there were an estimated 601,789 people living with thyroid cancer in the United States [1]. The age and gender-adjusted incidence of thyroid cancer has increased faster than that of any other malignancy in recent years, with the increased incidence seen in both genders and all ethnic backgrounds (figure 2 and figure 3) [2,3]. In women, however, the annual rate of increase has recently fallen from 4.2 percent per year from 1992 to 1999, and 6.9 percent per year from 1999 to 2009, to 2.2 percent per year from 2009 to 2011 [4].

The use of head and neck external beam radiation, commonly used to treat benign childhood conditions between 1910 and 1960, led to an increased incidence of thyroid cancer in the second half of the last century [5] (see "Radiation-induced thyroid cancer"). However, since radiation therapy for benign childhood conditions was largely abandoned in the 1950s to 1960s, it is unlikely that the increasing incidence in thyroid cancer seen in the last 10 to 15 years is associated with childhood radiation exposure. Some authors suggest that the increase in thyroid cancer in the United States and elsewhere may be primarily due to an increased detection of small papillary cancers secondary to more widespread use of neck ultrasonography and fine needle aspiration (FNA) of very small thyroid nodules [6-8].

Although the increasing incidence probably partially reflects earlier detection of subclinical disease (ie, small papillary cancers), an analysis of the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database found an increase in the rates of differentiated thyroid cancer of all sizes, including tumors greater than 4 cm [9,10].

The usual female-to-male ratio of papillary thyroid cancer is about 2.5:1, with most of the female preponderance occurring during the fourth and fifth decades of life. Although the incidence of thyroid cancer is rising, death rates (0.5 per 100,000 men and women per year) have not changed significantly between 2003 and 2012 [1].

                        

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References
Top
  1. http://seer.cancer.gov/statfacts/html/thyro.html (Accessed on April 08, 2016).
  2. Ries LAG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review 1975-2004, National Cancer Institute, Bethesda, MD. http://seer.cancer.gov/csr/1975_2004/ (Accessed on November 29, 2007).
  3. Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 2013; 105:175.
  4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5.
  5. Mack WJ, Preston-Martin S. Epidemiology of thyroid cancer. In: Thyroid Cancer, Fagin JA (Ed), Kluwer Academic Publishers, Boston 1998. p.1.
  6. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 2014; 140:317.
  7. Ahn HS, Kim HJ, Welch HG. Korea's thyroid-cancer "epidemic"--screening and overdiagnosis. N Engl J Med 2014; 371:1765.
  8. Vaccarella S, Franceschi S, Bray F, et al. Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. N Engl J Med 2016; 375:614.
  9. Enewold L, Zhu K, Ron E, et al. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol Biomarkers Prev 2009; 18:784.
  10. Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988-2005. Cancer 2009; 115:3801.
  11. Schneider AB, Sarne DH. Long-term risks for thyroid cancer and other neoplasms after exposure to radiation. Nat Clin Pract Endocrinol Metab 2005; 1:82.
  12. Pal T, Vogl FD, Chappuis PO, et al. Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study. J Clin Endocrinol Metab 2001; 86:5307.
  13. Hemminki K, Eng C, Chen B. Familial risks for nonmedullary thyroid cancer. J Clin Endocrinol Metab 2005; 90:5747.
  14. Nagataki S, Nyström E. Epidemiology and primary prevention of thyroid cancer. Thyroid 2002; 12:889.
  15. Boice JD Jr, Lubin JH. Occupational and environmental radiation and cancer. Cancer Causes Control 1997; 8:309.
  16. Antonelli A, Ferri C, Fallahi P, et al. Thyroid cancer in HCV-related chronic hepatitis patients: a case-control study. Thyroid 2007; 17:447.
  17. Rossing MA, Voigt LF, Wicklund KG, Daling JR. Reproductive factors and risk of papillary thyroid cancer in women. Am J Epidemiol 2000; 151:765.
  18. Fagin JA. How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy. J Endocrinol 2004; 183:249.
  19. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006; 6:292.
  20. Fagin JA, Mitsiades N. Molecular pathology of thyroid cancer: diagnostic and clinical implications. Best Pract Res Clin Endocrinol Metab 2008; 22:955.
  21. Jhiang SM, Sagartz JE, Tong Q, et al. Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas. Endocrinology 1996; 137:375.
  22. Knauf JA, Ma X, Smith EP, et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res 2005; 65:4238.
  23. McCarthy RP, Wang M, Jones TD, et al. Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas. Clin Cancer Res 2006; 12:2414.
  24. Shattuck TM, Westra WH, Ladenson PW, Arnold A. Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med 2005; 352:2406.
  25. Giannini R, Ugolini C, Lupi C, et al. The heterogeneous distribution of BRAF mutation supports the independent clonal origin of distinct tumor foci in multifocal papillary thyroid carcinoma. J Clin Endocrinol Metab 2007; 92:3511.
  26. Jung CK, Little MP, Lubin JH, et al. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab 2014; 99:E276.
  27. Faquin WC, Wong LQ, Afrogheh AH, et al. Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology. Cancer Cytopathol 2016; 124:181.
  28. Tielens ET, Sherman SI, Hruban RH, Ladenson PW. Follicular variant of papillary thyroid carcinoma. A clinicopathologic study. Cancer 1994; 73:424.
  29. Daniels GH. What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification. Endocr Pract 2011; 17:768.
  30. Ganly I, Wang L, Tuttle RM, et al. Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant. Hum Pathol 2015; 46:657.
  31. Rivera M, Ricarte-Filho J, Knauf J, et al. Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol 2010; 23:1191.
  32. Johnson TL, Lloyd RV, Thompson NW, et al. Prognostic implications of the tall cell variant of papillary thyroid carcinoma. Am J Surg Pathol 1988; 12:22.
  33. Ghossein R, Livolsi VA. Papillary thyroid carcinoma tall cell variant. Thyroid 2008; 18:1179.
  34. Asioli S, Erickson LA, Sebo TJ, et al. Papillary thyroid carcinoma with prominent hobnail features: a new aggressive variant of moderately differentiated papillary carcinoma. A clinicopathologic, immunohistochemical, and molecular study of eight cases. Am J Surg Pathol 2010; 34:44.
  35. Motosugi U, Murata S, Nagata K, et al. Thyroid papillary carcinoma with micropapillary and hobnail growth pattern: a histological variant with intermediate malignancy? Thyroid 2009; 19:535.
  36. Randolph GW, Duh QY, Heller KS, et al. The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. Thyroid 2012; 22:1144.
  37. Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994; 97:418.
  38. Eustatia-Rutten CF, Corssmit EP, Biermasz NR, et al. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab 2006; 91:313.
  39. Tuttle RM. Risk-adapted management of thyroid cancer. Endocr Pract 2008; 14:764.
  40. Zaydfudim V, Feurer ID, Griffin MR, Phay JE. The impact of lymph node involvement on survival in patients with papillary and follicular thyroid carcinoma. Surgery 2008; 144:1070.
  41. Voutilainen PE, Multanen MM, Leppäniemi AK, et al. Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 2001; 11:953.
  42. Hay ID, Bergstralh EJ, Goellner JR, et al. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 1993; 114:1050.
  43. Machens A, Holzhausen HJ, Dralle H. The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma. Cancer 2005; 103:2269.
  44. Pellegriti G, Scollo C, Lumera G, et al. Clinical behavior and outcome of papillary thyroid cancers smaller than 1.5 cm in diameter: study of 299 cases. J Clin Endocrinol Metab 2004; 89:3713.
  45. Ito Y, Kudo T, Kihara M, et al. Prognosis of low-risk papillary thyroid carcinoma patients: its relationship with the size of primary tumors. Endocr J 2012; 59:119.
  46. Casara D, Rubello D, Saladini G, et al. Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables. J Nucl Med 1993; 34:1626.
  47. Chiu AC, Delpassand ES, Sherman SI. Prognosis and treatment of brain metastases in thyroid carcinoma. J Clin Endocrinol Metab 1997; 82:3637.
  48. Robbins RJ, Wan Q, Grewal RK, et al. Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. J Clin Endocrinol Metab 2006; 91:498.
  49. Ghossein RA, Leboeuf R, Patel KN, et al. Tall cell variant of papillary thyroid carcinoma without extrathyroid extension: biologic behavior and clinical implications. Thyroid 2007; 17:655.
  50. Xing M, Westra WH, Tufano RP, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 2005; 90:6373.
  51. Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer 2007; 110:38.
  52. Kim TH, Park YJ, Lim JA, et al. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer 2012; 118:1764.
  53. Elisei R, Viola D, Torregrossa L, et al. The BRAF(V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study. J Clin Endocrinol Metab 2012; 97:4390.
  54. Melo M, da Rocha AG, Vinagre J, et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 2014; 99:E754.
  55. Liu X, Bishop J, Shan Y, et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer 2013; 20:603.
  56. Landa I, Ganly I, Chan TA, et al. Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab 2013; 98:E1562.
  57. Liu X, Qu S, Liu R, et al. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab 2014; 99:E1130.
  58. Klein M, Vignaud JM, Hennequin V, et al. Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. J Clin Endocrinol Metab 2001; 86:656.
  59. Yu XM, Lo CY, Lam AK, et al. Serum vascular endothelial growth factor C correlates with lymph node metastases and high-risk tumor profiles in papillary thyroid carcinoma. Ann Surg 2008; 247:483.
  60. Nikiforova MN, Kimura ET, Gandhi M, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 2003; 88:5399.
  61. Henderson YC, Shellenberger TD, Williams MD, et al. High rate of BRAF and RET/PTC dual mutations associated with recurrent papillary thyroid carcinoma. Clin Cancer Res 2009; 15:485.
  62. Ricarte-Filho JC, Ryder M, Chitale DA, et al. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res 2009; 69:4885.
  63. Xing M, Liu R, Liu X, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol 2014; 32:2718.
  64. Nikiforova MN, Wald AI, Roy S, et al. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. J Clin Endocrinol Metab 2013; 98:E1852.
  65. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA 2013; 309:1493.
  66. Cappola AR, Mandel SJ. Molecular testing in thyroid cancer: BRAF mutation status and mortality. JAMA 2013; 309:1529.
  67. Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric papillary thyroid carcinoma. Ann Surg Oncol 2009; 16:2609.
  68. Leboulleux S, Rubino C, Baudin E, et al. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab 2005; 90:5723.